US 2023/0399415 A1 · Twin Immune Cell Engager

Abstract

A Twin Immune Cell Engager (TWICE) is a kit or composition for treating cancer comprising a first component and second component. Each component comprises a targeting moiety that binds a tumor antigen expressed by the cancer or an antigen expressed by a non-cancer cell in the tumor microenvironment. In some embodiments, the first and second components each comprise an immune cell binding domain capable of immune cell binding activity when binding the immune cell binding domain in the other component, and a complementary binding domain capable of binding to a complementary antigen when binding the complementary binding domain in the other component. In some embodiments, the first and/or second components comprise a complementary functional domain with activity when targeted to the cancer cell or its microenvironment. The present TWICE complexes offer a unique ability to combine multiple functions into a two-component complex that becomes activated in the tumor microenvironment. The present complexes, thus, provide meaningful advantages in having a single approach to administering a two-component complex that is localized to the tumor microenvironment and has the ability to effect two different signals to benefit patients. This unique construct offers benefits that were not present in prior art constructs.

Claims20

Dependent claims

1-25. (canceled)

A kit or composition for treating cancer in a patient comprising:

a. a first component comprising a targeted immune cell binding agent comprising:
i. a first targeting moiety that binds a tumor antigen expressed by the cancer;
ii. a first immune cell binding domain capable of immune cell binding activity when binding a second immune cell binding domain, wherein the second immune cell binding domain is not part of the first component, and wherein the first immune cell binding domain is either a VH domain or VL domain;
iii. a first inert binding partner for the first immune cell binding domain, wherein the first inert binding partner binds to the first immune cell binding domain such that the first immune cell binding domain does not bind to the second immune cell binding domain unless the inert binding partner is removed, wherein if the first immune cell binding domain is a VH domain, the inert binding partner is a VL domain and if the first immune cell binding domain is a VL domain, the inert binding partner is a VH domain;
iv. a protease cleavage site separating the first immune cell binding domain and the first inert binding partner, wherein the protease cleavage site is capable of releasing the inert binding partner from the immune cell binding domain in the presence of a protease:
(1) expressed by the cancer or a tumor microenvironment cell;
or
(2) colocalized to the cancer by a targeting moiety that is an antibody or antigen binding fragment thereof that binds (a) a tumor antigen expressed by the cancer and that is the same or different from the first and/or second targeting moiety in the agent or (b) an antigen expressed by a cell in the tumor microenvironment;
and
v. a first complementary functional domain capable of immune cell binding, and:
b. a second component comprising a targeted immune cell binding agent comprising:
i. a second targeting moiety;
ii. a second immune cell binding domain;
and
iii. optionally a second complementary functional domain capable of immune cell binding.

12 more elements

Dependencies are inferred from the claim text.

Twin Immune Cell Engager

Life of this patent

Twin Immune Cell Engager

Life of this patent

Abstract

Claims20